The cell biology, biochemistry and immunology of Leishmania and Trypanosoma are investigated as models of intra- and extracellular parasitism, respectively. As all interactions between host and parasite occur, at least temporarily, at the level of the parasite surface membrane, thus emphasis is place on: 1) integrated structural, biochemical and antigenic characterization of the intact and isolated parasite surface membrane (SM) and parasite released products and 2) defining the mechanisms by which parasites survive and circumvent host-defense systems. To those ends, various studies are employed involving: Subcellular fractionation, fine structure labeling and localization, radiolabeling, electrophoresis and chromatography assays, immuno-binding and labeling assays and in vitro culture. Using such techniques, the major SM components/antigens of Leishmania sp. and procyclic Trypanosoma rhodesiense were identified. The major SM antigens to which leishmaniasis patients make IgG responses were delineated. Total lipid composition of Leishmania SM was determined and 3 SM phospholipases identified. Five phosphomonesterases were identified, partially characterized and localized cytochemically in the Leishmania SM. The SM origin and characterization of 7 Leishmania-released antigens was demonstrated. Leishmania SM-antigen specific murine T-cell clones were generated which passively produced DTH responses in mice and macrophage-activating lymphokines in vitro. Monoclonal antibodies and C-DNA libraries were made for isolation of SM antigens and their genes. The kinetics and mechanisms of Leishmania SM sugar and amino acid transport were investigated. Both a SM-proton pump and a specific [H+] ATPase were demonstrated. The former providing the electro-chemical potential for SM transport in this organism. These results underscore the relevance of the surface membrane to parasite survival and the need for its biochemical and immunochemical characterization. The goals of this project are to provide fundamental bases for understanding the mechanisms of parasite survival.